A. Haraldsson

C. M. R. Weemaes

F. Preijers

G. A. M. de Vaan

I. S. Klasen

J. A. J. M. Bakkeren

English

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CD4 deficiencyC. M. R. Weemaes
& A.eM.rde vaan in myelodysplastic syndrome
J. A. J, M. Bakkeren 
L S, Klasen 
A. Haraldsson
with monosomy 7
Received: 20 January 1995 
Accepted: 26 April 1995
C. Weemaes (Ë3) • G. A. M. de Vaan 
J. A. J. M. Bakkeren 
Department of Paediatrics,
University Hospital Nijmegen,
PO Box 9101, 6500 HB Nijmegen,
The Netherlands 
Fax: 080-616428
F. Preijers
Department of Haematology,
University of Nijmegen,
The Netherlands
I. S. Klasen
Department of Clinical Chemistry, 
University of Nijmegen, The Netherlands
A. Haraldsson 
Department of Paediatrics,
National University of Iceland, 
Reykjavik, Iceland
Abstract We describe a patient with 
myelodysplastic syndrome with 
monosomy 7 presenting with a T-cell 
defect. He suffered from infections 
from the age of 10 years, when a 
CD4 deficiency and impaired lym- 
phoproliferative responses in vitro 
were found. The only symptom of a 
myelodysplastic syndrome at that 
time was thrombocytopenia with gi­
ant platelets. Monosomy 7 was 
found in the bone marrow cells. At 
the age of 11 years he developed 
other characteristics of monosomy 7 
including splenomegaly and 
anaemia. Some months later 
leukaemia was diagnosed.
Conclusion In non-HIV CD4 defi­
ciency myelodysplastic syndrome 
has to be considered.
Key words CD4 deficiency * 
Myelodysplastic syndrome • 
Monosomy 7 • Immunodeficiency
Abbreviations FCM  flow 
cytometric analysis * MDS 
myelodysplastic syndrome
Introduction
Characteristic features in myelodysplastic syndrome (MDS) 
with monosomy 7 include recurrent infections, hepato- 
splenomegaly, lymphadenopathy, (refractory) anaemia, 
thrombocytopenia, leucocytosis and a hypercellular bone 
marrow with a slight increase in blast cells. Acute mye­
loid leukaemia is likely to develop as a terminal event [5], 
Monosomy 7 does not usually affect lymphoid subpopula­
tions but is restricted to committed progenitor cells with 
the capacity to differentiate into mature myeloid cells [2 ]. 
We report a patient with MDS presenting with a T-cell de­
fect.
Case report
The patient, a boy, suffered from recurrent upper and lower respi­
ratory tract infections (both otitis media and pneumonia) from the 
age of 10 years. He had once developed a parotitis due to staphy­
lococci and had extended warts.
On admission at the age of 10.5 years he had enormous warts 
on his feet and fingers. No other abnormalities were noted on 
physical examination. WBC and haemoglobin were normal (Table 
1). Platelets were unusually large and decreased in number (Table 
1). Serum immunoglobins were normal (Table 1). HIV test was 
negative, Immunophenotyping by flowcytometric analysis (FCM) 
of peripheral blood T-cells revealed 44% CD3+ cells (1.60 x  1G9/1) 
of which were only 13% CD4+ cells (0.46 x  109/l) and 32% CD8+ 
cells (1.14 x  109/1), resulting in a reversed T4/T8-ratio (0.4).
Proliferative responses to phytohaemagglutinin and poke weed 
mitogen were impaired (Table 1). Monosomy 7 could not be 
demonstrated in the phytohaemagglutinin-stimulated cells.
97
Table 1 Haematological and 
immunological studies in the 
patient {PHA phytohaemagglu- 
tinin, PWM pokeweed mito­
gen)
Age in years
10 11
7/12 9/12 10/12 0 1/12 3/12
Haematological studies
Hb g/dl 13.1 12.9 12.0 10.6 10.2 7.0
Platelets 109/l 64 153 80 103 59 16
WBC 1071 8.7 32.5 10.2 32.8 19.6 30.0
Blasts % 12 10 20
Neutrophils % 36 50 23 19 28 22
Precursors % 1 15 2 26 14 14
Lymphocytes % 40 9 5 5 16 12 21
Monocytes % 23 24 20 27 36 21
Eosinophils % 2
Bone marrow Myelomonocytic
hyperplasia
lymphopenia
Unchanged Unchanged
Blasts % 4 2 6 16
Karyotype 45 XY, -7
Immunological studies
CD3+ cells 109/1 1.60 2.88 1.44
CD4+ cells 109/1 0.46 0.61 • 0.27
CD8+ cells 10y/i 1.14 1.44 0.96
CD4/CD8 ratio 0.4 0.4 0.3
Lymphocyte pro­
liferation in vitro
(% of controls) to
PHA 2 0 %
PWM 25%
Serum immuno-globulins
IgG g/i 7.30 5.82 5.36
IgA g/1 0.92 0.68 0.54
IgM g/1 1.30 1.08 0.84
IgD IU/1 12 7
IgE IU/1 12
•
6
Table 2 Immunophenotyping of peripheral blood cells of the pa­
tient at the age of 11 years. Peripheral blood was anti-coagulated 
with EDTA. Cell samples were stained single or double with im- 
munofluorescing FITC- or PE-labelled monoclonal antibodies ac­
cording to the full blood method. Expression of varying antigens 
was determined by flow cytometry in a Coulter Epics Elite. Cell
populations were divided in two clusters based on forward and side 
vscatters. Cluster 1 (Gate A) contained a very immature populations 
of CD 13, 33, 34, 36 positive cells. Cluster 2 (Gate B) contained a 
more mature myeloid population of CD 13, 14, 15, 33 positive, 
CD34 negative cells
Gate A
Nucleated cells: 21%
Gate B
Nucleated cells: 59%
CD2 42% CD 13 45% CD2 8 % CD13 90%
CD 3 38% CD14 11% CD 3 7% CD14 59%
CD4 8% CD 15 11% CD 15 95%
CD8 19% CD33 51% CD33 99%
CD4/CD45RA 4% CD34 55% CD34 16%
CD4/CD45RO 3% CD36 36% CD36
CD3/CD57 4% CD42 2 0 % CD42 34%
T4/T8-ratio = 0.4
CD19 3% CD56 16% CD19 1%
98
Bone marrow study revealed no leukaemia but was compatible 
with MDS. Monosomy 7 was demonstrated by cytogenetic studies 
of bone marrow cells.
At the age of 10 years and 9 months the boy again suffered 
from pneumonia and had to be treated with antibiotics, At that time 
he had a leukocytosis with some blasts and immature myeloid cells 
in peripheral blood (Table 1), He recovered rapidly and his white 
blood cells became normal again. However, within some months 
splenomegaly developed. At the age of 11 years haematological 
studies revealed a slight decrease of haemoglobin to 10.6 g/dl, 
WBC was increased with metamyelocytes 15% and blasts 12%. T- 
cell markers were comparable to earlier studies: CD3+ cells 38%, 
CD4+ cells 8% and CD8+ cells 19% as determined by FCM 
(Table 2). However, the absolute number of CD4+ cells was only 
marginally decreased according to age (Table 1). Further analysis 
of this cell population revealed high percentages of CD34, CD33, 
CD 13 and CD36 positive cells (Table 2). These results suggested 
the presence of an early myeloid progenitor population in the pe­
ripheral blood of this patient.
At the age of 11 years and 3 months he became anaemic. CD4 
deficiency was again present (Table 1). Bone marrow studies now 
revealed a high percentage of blast cells (Table 1) raising the sus­
picion of a developing leukaemia. He was initially treated with cy­
tostatics. Recently a bone marrow transplantation was performed.
Discussion
The clinical sym ptom s o f this patient are similar to those 
found in immunodeficiency* T he laboratory findings of 
this patient, particularly  the decreased num ber o f  CD4+ 
cells attended w ith  the impaired lyphoproliferative stim u­
lation tests are strongly  rem iniscent o f  H IV  infection as 
are the unusual verrucous reactions [4]. However, HIV 
tests remained negative. The boy suffered  from M D S with 
m onosom y 7. R ecurren t acute infections, often resulting
in significant morbidity and mortality are a prominent fea­
ture of M D S [2, 3], The increased susceptibility to infec­
tions in patients with MDS is thought to be due to neu­
tropenia or functional defects o f neutrophils. Neutrophil 
function tests sometimes reveal defective chemotaxis with 
reduced killing despite a normal nitrozolium blue test. 
The clinical symptoms in our patient were those o f  a T- 
cell defect and preceded the anaem ia and the leukaemic 
stage of the disease.
A bnorm alities in T-lymphocytes, namely an imbalance 
betw een both  m ajor T-cell subsets and a reduced prolifer­
ative response to  mitogenic stimulation, have been de­
scribed in M DS patients [1]. In this study only patients 
who had either a  cytopenia affecting one or more o f  the 
peripheral m yelo id  lines or a peripheral monocytosis were 
investigated. M ost of them had already refractory anaemia 
and som e had  developed chronic myelomonocytic leu­
kaemia. The boy presented here with m onosom y 7 w as in­
vestigated in an earlier stage of the disease and did not 
have a cytopenia. W hether his lym phocyte abnormalities 
represent a prim ary defect of the lymphocytes is not clear. 
In the lym phocytes cultured in vitro with phytohaemag- 
glutinin m onosom y 7 has not been demonstrated. A t that 
time not only the CD4 deficiency was present but the 
platelets w ere  also decreased in num ber and were of giant 
size. In  the patient presented a T-cell defect was present 
before the characteristic features o f M DS e.g. (refractory) 
anaemia and hepatosplenomegaly developed. Only the 
throm bocytopenia pointed to the diagnosis of MDS. We 
suggest tha t in non-HIV CD4 deficiency MDS m ight be 
causally related to the T-cell defect.
References
l.Bynoe AG, Scott CS, Ford P, Roberts 
BE (1983) Decreased T helper cells in 
the myelodysplastic syndromes. Br J 
Haematol 54: 97-102
2. Gerritsen WR> Donahue J, Bauman J, 
Jhanwar SC r Keman NA, Castro- 
Maiaspina H, O ’Reilly RG, Bourhis JH 
(1992) Clonal analysis of myelodysplas­
tic syndrome: monosomy 7 is expressed 
in the myeloid lineage, but not in lym­
phoid lineage as detected by fluorescent 
in situ hybridization. Blood 80: 217-224 
3-Koeffler HP, Golde DW (1980) Human 
preleukaemia. Ann Int Med 93: 347-353
4. LeBoit PE (1992) Dermatopathologic 
findings in patients infected with HIV. 
Dermatol Clin 10: 59-71
5. Sieff CA, Chessells JM, Harvey AM, 
Pickthall VJ, Lawler SD (1981) Mono­
somy 7 in childhood: a myeloprolifera­
tive disorder. Br J Haematol 49:
235-249


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CD4 deficiency in myelodysplastic syndrome with monosomy 7

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